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assessing the viral fitness of oseltamivir-resistant influenza viruses in ferrets, using a competitive-mixtures model.to determine the relative fitness of oseltamivir-resistant strains compared to susceptible wild-type viruses, we combined mathematical modeling and statistical techniques with a novel in vivo "competitive-mixtures" experimental model. ferrets were coinfected with either pure populations (100% susceptible wild-type or 100% oseltamivir-resistant mutant virus) or mixed populations of wild-type and oseltamivir-resistant influenza viruses (80%:20%, 50%:50%, and 20%:80%) at equivalent infectivity tite ...201020631138
mapping primary gyrogenesis during fetal development in primate brains: high-resolution in utero structural mri of fetal brain development in pregnant baboons.the global and regional changes in the fetal cerebral cortex in primates were mapped during primary gyrification (pg; weeks 17-25 of 26 weeks total gestation). studying pregnant baboons using high-resolution mri in utero, measurements included cerebral volume, cortical surface area, gyrification index and length and depth of 10 primary cortical sulci. seven normally developing fetuses were imaged in two animals longitudinally and sequentially. we compared these results to those on pg that from t ...201020631812
properly folded bacterially expressed h1n1 hemagglutinin globular head and ectodomain vaccines protect ferrets against h1n1 pandemic influenza virus.in the face of impending influenza pandemic, a rapid vaccine production and mass vaccination is the most effective approach to prevent the large scale mortality and morbidity that was associated with the 1918 "spanish flu". the traditional process of influenza vaccine production in eggs is time consuming and may not meet the demands of rapid global vaccination required to curtail influenza pandemic.201020634959
the eurocine l3 adjuvants with subunit influenza antigens induce protective immunity in mice after intranasal vaccination.the immunogenicity and protective efficacy in mice of intranasally (i.n.) administrated influenza subunit antigens together with lipid-based adjuvants (eurocine) were compared to those of subcutaneous (s.c.) immunisation. influenza hemagglutination inhibition (hai) and elisa igg titers were similar in the group's vaccinated s.c. and after i.n. vaccination with adjuvants. the virus-specific iga levels in serum were higher after vaccination i.n. with adjuvant than after s.c immunisation. virus-spe ...201020637767
the non-lemniscal auditory cortex in ferrets: convergence of corticotectal inputs in the superior colliculus.descending cortical inputs to the superior colliculus (sc) contribute to the unisensory response properties of the neurons found there and are critical for multisensory integration. however, little is known about the relative contribution of different auditory cortical areas to this projection or the distribution of their terminals in the sc. we characterized this projection in the ferret by injecting tracers in the sc and auditory cortex. large pyramidal neurons were labeled in layer v of diffe ...201020640247
an abc transporter and a tonb ortholog contribute to helicobacter mustelae nickel and cobalt acquisition.the genomes of helicobacter species colonizing the mammalian gastric mucosa (like helicobacter pylori) contain a large number of genes annotated as iron acquisition genes but only few nickel acquisition genes, which contrasts with the central position of nickel in the urease-mediated acid resistance of these gastric pathogens. in this study we have investigated the predicted iron and nickel acquisition systems of the ferret pathogen helicobacter mustelae. the expression of the outer membrane pro ...201020643857
deep brain stimulation results in local glutamate and adenosine release: investigation into the role of astrocytes.several neurological disorders are treated with deep brain stimulation; however, the mechanism underlying its ability to abolish oscillatory phenomena associated with diseases as diverse as parkinson's disease and epilepsy remain largely unknown.201020644423
induction of broadly neutralizing h1n1 influenza antibodies by vaccination.the rapid dissemination of the 2009 pandemic influenza virus underscores the need for universal influenza vaccines that elicit protective immunity to diverse viral strains. here, we show that vaccination with plasmid dna encoding h1n1 influenza hemagglutinin (ha) and boosting with seasonal vaccine or replication-defective adenovirus 5 vector encoding ha stimulated the production of broadly neutralizing influenza antibodies. this prime/boost combination increased the neutralization of diverse h1n ...201020647428
a novel model of lethal hendra virus infection in african green monkeys and the effectiveness of ribavirin treatment.the henipaviruses, hendra virus (hev) and nipah virus (niv), are emerging zoonotic paramyxoviruses that can cause severe and often lethal neurologic and/or respiratory disease in a wide variety of mammalian hosts, including humans. there are presently no licensed vaccines or treatment options approved for human or veterinarian use. guinea pigs, hamsters, cats, and ferrets, have been evaluated as animal models of human hev infection, but studies in nonhuman primates (nhp) have not been reported, ...201020660198
focusing attention on sound.a new study finds that neurons in the ferret frontal cortex typically respond to sound only during trained auditory tasks and that these neurons depict the task-related meaning rather than the acoustical properties of stimuli.201020661266
oseltamivir-resistant pandemic a/h1n1 virus is as virulent as its wild-type counterpart in mice and ferrets.the neuraminidase inhibitor oseltamivir is currently used for treatment of patients infected with the pandemic a/h1n1 (ph1n1) influenza virus, although drug-resistant mutants can emerge rapidly and possibly be transmitted. we describe the characteristics of a pair of oseltamivir-resistant and oseltamivir-susceptible ph1n1 clinical isolates that differed by a single change (h274y) in the neuraminidase protein. viral fitness of ph1n1 isolates was assessed in vitro by determining replication kineti ...201020661429
an influenza a/h1n1/2009 hemagglutinin vaccine produced in escherichia coli.the a/h1n1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. platforms based on virus culture in mammalian or insect cells are currently under investigation. alternatively, expression of fragments of the hemagglutinin (ha) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. despite experimental evidence on th ...201020661476
expression of biologically active recombinant ferret (mustela putorius furo) interleukin-8 from escherichia coli.the authors expressed recombinant ferret interleukin-8 protein (rfril-8) in escherichia coli as a glutathione-s-transferase fusion protein. western blot analyses revealed that anti-ovine il-8 antibody reacted with rfril-8 at 10 kda. to confirm that the rfril-8 was biologically active, the authors examined chemotaxis and respiratory burst activity of ferret polymorphonuclear blood cells (pmns) exposed to rfril-8. the rfril-8 strongly induced chemotactic and respiratory burst activities in a stati ...201020678809
the superior colliculus of the ferret: cortical afferents and efferent connections to dorsal thalamus.by injecting both biotinylated and fluorescent dextran amines into the superior colliculus of the ferret we traced its afferent connections from the cerebral cortex and its projections to nuclei of the dorsal thalamus. all visual and auditory cortical areas had retrogradely labelled layer 5 pyramidal neurons projecting to the superior colliculus, with the highest density in areas 18 and 21. secondary somatosensory and motor cortical regions also projected to the superior colliculus. no retrograd ...201020682301
advanced diagnostic approaches and current medical management of insulinomas and adrenocortical disease in ferrets (mustela putorius furo).endocrine neoplasia is the most common tumor type in domestic ferrets, especially in middle-aged to older ferrets. islet cell tumors and adrenocortical tumors constitute the major types of endocrine neoplasms. insulinoma is a tumor that produces and releases excessive amounts of insulin. evaluation of fasted blood glucose levels provides a quick diagnostic assessment for the detection of insulinomas. use of glucocorticoids, diazoxide, and diet modification are some of the medical treatment optio ...201020682429
ferret coronavirus-associated diseases.a novel coronavirus of ferrets was first described in 1993. this coronavirus caused an enteric disease called epizootic catarrhal enteritis (ece). recently, a ferret systemic coronavirus (frscv)-associated disease was discovered. this new systemic disease resembles the dry form of feline infectious peritonitis (fip) and has been reported in the united states and europe. this article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret fip-lik ...201020682435
disseminated idiopathic myofasciitis in ferrets.first described in 2003, disseminated idiopathic myofasciitis (dim) has emerged as a new disease in young, domestic ferrets. dim is a severe inflammatory condition that affects primarily muscles and surrounding connective tissues. the disease is characterized by rapid onset of clinical signs, high fever, neutrophilic leukocytosis, and general lack of response to therapeutic intervention. until recently dim was considered fatal, but a few surviving ferrets indicate there may be an effective treat ...201020682436
henipavirus: a review of laboratory animal pathology.the genus henipavirus contains two members-hendra virus (hev) and nipah virus (niv)-and each can cause fatal disease in humans and animals. hev and niv are currently classified as biosafety level 4, and niv is classified as a category c priority pathogen. the aim of this article is to discuss the pathology of laboratory animal models of henipavirus infection and to assess their suitability as animal models for the development and testing of human therapeutics and vaccines. there has been conside ...201020682803
comparative pathology of select agent influenza a virus infections.influenza a virus infections may spread rapidly in human populations and cause variable mortality. two of these influenza viruses have been designated as select agents: 1918 h1n1 virus and highly pathogenic avian influenza (hpai) virus. knowledge of the pathology of these virus infections in humans, other naturally infected species, and experimental animals is important to understand the pathogenesis of influenza, to design appropriate models for evaluation of medical countermeasures, and to mak ...201020682805
expression and distribution of voltage-gated ion channels in ferret sinoatrial node.spontaneous diastolic depolarization in the sinoatrial (sa) node enables it to serve as pacemaker of the heart. the variable cell morphology within the sa node predicts that ion channel expression would be heterogeneous and different from that in the atrium. to evaluate ion channel heterogeneity within the sa node, we used fluorescent in situ hybridization to examine ion channel expression in the ferret sa node region and atrial appendage. sa nodal cells were distinguished from surrounding cardi ...201020682846
recombinant soluble, multimeric ha and na exhibit distinctive types of protection against pandemic swine-origin 2009 a(h1n1) influenza virus infection in ferrets.the emergence and subsequent swift and global spread of the swine-origin influenza virus a(h1n1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. with this aim, we produced soluble, multimeric forms of the 2009 a(h1n1) ha (sha(3)) and na (sna(4)) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. immunization twice with 3.75-microg doses of these antigens e ...201020686020
oseltamivir-resistant pandemic h1n1/2009 influenza virus possesses lower transmissibility and fitness in ferrets.the neuraminidase (na) inhibitor oseltamivir offers an important immediate option for the control of influenza, and its clinical use has increased substantially during the recent h1n1 pandemic. in view of the high prevalence of oseltamivir-resistant seasonal h1n1 influenza viruses in 2007-2008, there is an urgent need to characterize the transmissibility and fitness of oseltamivir-resistant h1n1/2009 viruses, although resistant variants have been isolated at a low rate. here we studied the trans ...201020686654
ferret badger rabies origin and its revisited importance as potential source of rabies transmission in southeast china.the frequent occurrence of ferret badger-associated human rabies cases in southeast china highlights the lack of laboratory-based surveillance and urges revisiting the potential importance of this animal in rabies transmission. to determine if the ferret badgers actually contribute to human and dog rabies cases, and the possible origin of the ferret badger-associated rabies in the region, an active rabies survey was conducted to determine the frequency of rabies infection and seroprevalence in d ...201020691095
behavioral measures of auditory streaming in ferrets (mustela putorius).an important aspect of the analysis of auditory "scenes" relates to the perceptual organization of sound sequences into auditory "streams." in this study, we adapted two auditory perception tasks, used in recent human psychophysical studies, to obtain behavioral measures of auditory streaming in ferrets (mustela putorius). one task involved the detection of shifts in the frequency of tones within an alternating tone sequence. the other task involved the detection of a stream of regularly repeati ...201020695663
electrodiagnostic examination of the tibial nerve in clinically normal ferrets.tibial nerves of 10 normal domestic ferrets (mustela putorius furo) were evaluated by means of electrodiagnostic tests: motor nerve conduction studies (mncss), supramaximal repetitive nerve stimulation (srns), f waves, and cord dorsum potentials (cdps). values of conduction velocity, proximal and distal compound muscular action potentials, and amplitudes of mncs were, respectively, 63.25 +/- 7.56 m/sec, 10.79 +/- 2.75 mv, and 13.02 +/- 3.41 mv. mean decrements in amplitude and area of compound m ...201020706690
diagnosis and treatment of myelo-osteolytic plasmablastic lymphoma of the femur in a domestic ferret.a 6-year-old 0.82-kg (1.8-lb) spayed female domestic ferret was evaluated because of a 1-month history of decreased activity that had progressively worsened over the past week. the ferret had previously been determined to have adrenocortical disease and was undergoing medical management for the associated clinical signs.201020707751
protection of ferrets from infection by swine-origin 2009 a (h1n1) influenza virus by the inactivated vaccine.swine-origin pandemic 2009 a (h1n1) influenza viruses are still infecting humans, and humans are currently being vaccinated with the inactivated vaccine of 2009 a (h1n1) influenza virus. we wanted to determine the efficacy of 2009 a (h1n1) inactivated vaccine in ferrets. ferrets immunized with one dose (7.5 microg) of 2009 a (h1n1) inactivated vaccine were not protected from infections of either pandemic h1n1 or seasonal h1n1 influenza viruses, while ferrets immunized with two doses of 2009 a (h ...201020712484
multiple infections with seasonal influenza a virus induce cross-protective immunity against a(h1n1) pandemic influenza virus in a ferret model.an age bias toward children and young adults has been reported for infection and hospitalizations with pandemic h1n1 influenza (a[h1n1]pdm) in the 2009 and 2010 influenza seasons in the southern and northern hemispheres. serological analysis of prepandemic samples has shown a higher incidence of cross-reactive antibodies to a(h1n1)pdm virus in older populations; conserved t cell epitopes between viruses have been identified. the contribution of preexisting immunity to seasonal influenza to prote ...201020715930
evaluation of a modified vaccinia virus ankara (mva)-based candidate pandemic influenza a/h1n1 vaccine in the ferret model.the zoonotic transmissions of highly pathogenic avian influenza viruses of the h5n1 subtype that have occurred since 1997 have sparked the development of novel influenza vaccines. the advent of reverse genetics technology, cell-culture production techniques and novel adjuvants has improved the vaccine strain preparation, production process and immunogenicity of the vaccines, respectively, and has accelerated the availability of pandemic influenza vaccines. however, there is still room for improv ...201020719991
multiple progressive piloleiomyomas in a ferret (mustela putorius furo): a case report.a 2.5-year-old ovariectomized female ferret developed multiple progressive linear and raised nodules on the skin. the first lesions occurred on the tail, which was then amputated. over the following 3 years, additional lesions appeared in the vicinity of the scar and then further rostrally on the flanks and thorax. histological and immunohistochemical investigation led to a diagnosis of multiple piloleiomyomas. the unique characteristics of this ferret disease are described and compared with tho ...201120723189
[effect of the 5-ht3 receptor antagonist granisetron on estramustine phosphate sodium (estracyt)-induced emesis in ferrets].estracyt(r) is an antimitotic drug used for the treatment of prostate cancer, and its most common adverse effects are nausea and vomiting. in this study, we investigated the effect of a 5-ht3 receptor antagonist, granisetron, on emesis induced in ferrets by estramustine phosphate sodium (emp), the active ingredient of estracyt. to clarify the mechanism of action of emp-induced emesis, we also investigated the effect of emp on the release of serotonin (5-ht) in the isolated rat ileum. emp (3 mg/k ...201020724808
using electron beam radiation to simulate the dose distribution for whole body solar particle event proton exposure.as a part of the near solar system exploration program, astronauts may receive significant total body proton radiation exposures during a solar particle event (spe). in the center for acute radiation research (carr), symptoms of the acute radiation sickness syndrome induced by conventional radiation are being compared to those induced by spe-like proton radiation, to determine the relative biological effectiveness (rbe) of spe protons. in an spe, the astronaut's whole body will be exposed to rad ...201020725839
viremia associated with fatal outcomes in ferrets infected with avian h5n1 influenza virus.avian h5n1 influenza viruses cause severe disease and high mortality in infected humans. however, tissue tropism and underlying pathogenesis of h5n1 virus infection in humans needs further investigation. the objective of this work was to study viremia, tissue tropism and disease pathogenesis of h5n1 virus infection in the susceptible ferret animal model. to evaluate the relationship of morbidity and mortality with virus loads, we performed studies in ferrets infected with the h5n1 strain a/vn/12 ...201020730085
cannabinoid-induced reduction in antral pacemaker frequency: a telemetric study in the ferret.the gastric myoelectric activity (gma) is the electrical pacesetter potential, which drives gastric motility. cannabinoids have broad-spectrum antiemetic and antinauseant activity. paradoxically, they inhibit intestinal peristalsis and reduce gastric motility but their effect on gma remains unknown.201020731777
oseltamivir-resistant variants of the 2009 pandemic h1n1 influenza a virus are not attenuated in the guinea pig and ferret transmission models.oseltamivir is routinely used worldwide for the treatment of severe influenza a virus infection, and should drug-resistant pandemic 2009 h1n1 viruses become widespread, this potent defense strategy might fail. oseltamivir-resistant variants of the pandemic 2009 h1n1 influenza a virus have been detected in a substantial number of patients, but to date, the mutant viruses have not moved into circulation in the general population. it is not known whether the resistance mutations in viral neuraminid ...201020739532
transgenic animals may help resolve a sticky situation in cystic fibrosis.cystic fibrosis (cf) is caused by defects in the cftr, a camp-activated cl- channel of epithelia. the resulting reduction in epithelial fluid transport creates abnormally viscous secretions from airway mucous glands that may be a major factor in cf pathology. mouse airways have few mucous glands, and the mouse model of cf exhibits no significant airway disease. pigs and ferrets, however, have approximately the same number of airway mucous glands as humans. in this issue of the jci, three indepen ...201020739746
disease phenotype of a ferret cftr-knockout model of cystic fibrosis.cystic fibrosis (cf) is a recessive disease that affects multiple organs. it is caused by mutations in cftr. animal modeling of this disease has been challenging, with species- and strain-specific differences in organ biology and cftr function influencing the emergence of disease pathology. here, we report the phenotype of a cftr-knockout ferret model of cf. neonatal cftr-knockout ferrets demonstrated many of the characteristics of human cf disease, including defective airway chloride transport ...201020739752
analgesic effect of bupivacaine eluting porcine small intestinal submucosa (sis) in ferrets undergoing acute abdominal hernia defect surgery.porcine small intestinal submucosa (sis) is used as a biological implant for abdominal wall hernia repair to facilitate wound healing and augment local tissue strength. this prospective, randomized, blinded study evaluated local pain control provided by bupivacaine adsorbed to sis for repair of acutely created abdominal wall full thickness muscle/fascial defects in ferrets.201120797732
production and antigenic properties of influenza virus from suspension mdck-siat7e cells in a bench-scale bioreactor.in efforts to overcome limitations associated with egg-based influenza vaccines, mammalian cell substrates have gradually emerged as potential production platforms. recently, a suspension madin darby canine kidney (mdck) cell line for influenza virus production was created by expressing the human siat7e gene. to examine the broad susceptibility of this novel cell line, the scalability of the production process, and the antigenic stability of cell-derived progeny viruses, infection experiments us ...201020800699
natural cases of 2009 pandemic h1n1 influenza a virus in pet ferrets.respiratory swab samples were collected from 5 pet ferrets (mustela putorius furo) exhibiting influenza-like illness. the ferrets represented 3 households in 2 states. in each case, the owners reported influenza-like illness in themselves or family members prior to the onset of a similar illness in the ferrets. real-time reverse transcription polymerase chain reaction assays designed for the detection of the 2009 h1n1 influenza a virus were conducted in the state animal health laboratories. the ...201020807944
a live attenuated h7n7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets, and monkeys.a live attenuated h7n7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (ha) and neuraminidase (na) genes of highly pathogenic (hp) a/netherlands/219/03 (nl/03) (h7n7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) a/ann arbor/6/60 ca (aa ca) (h2n2) virus. the reassortant h7n7 nl/03 ca vaccine virus was temperature sensitive and attenuated in mice, ferrets, and african green monkeys (agms). intranasal (i.n.) administrati ...201020810733
p/q and n channels control baseline and spike-triggered calcium levels in neocortical axons and synaptic boutons.cortical axons contain a diverse range of voltage-activated ion channels, including ca(2+) currents. interestingly, ca(2+) channels are not only located at presynaptic terminals, but also in the axon initial segment (ais), suggesting a potentially important role in the regulation of action potential generation and neuronal excitability. here, using two-photon microscopy and whole-cell patch-clamp recording, we examined the properties and role of calcium channels located in the ais and presynapti ...201020810905
influenza enhances susceptibility to natural acquisition of and disease due to streptococcus pneumoniae in ferrets.the role of respiratory viruses in the transmission of streptococcus pneumoniae is poorly understood. key questions, such as which serotypes are most fit for transmission and disease and whether influenza virus alters these parameters in a serotype-specific manner, have not been adequately studied. in a novel model of transmission in ferrets, we demonstrated that pneumococcal transmission and disease were enhanced if donors had previously been infected with influenza virus. bacterial titers in n ...201020822454
use of a business excellence model to improve conservation programs.the current shortfall in effectiveness within conservation biology is illustrated by increasing interest in "evidence-based conservation," whose proponents have identified the need to benchmark conservation initiatives against actions that lead to proven positive effects. the effectiveness of conservation policies, approaches, and evaluation is under increasing scrutiny, and in these areas models of excellence used in business could prove valuable. typically, conservation programs require years ...201020825449
nasal turbinate enlargement due to cartilage and bone proliferation: a normal developmental finding in young ferrets.toxicity studies of intranasally administered, live attenuated influenza virus vaccine candidates conducted in male and female ferrets led to the microscopic observation of individual differences in the size of nasal turbinates, especially in the dorsal aspect of the nasal cavity. the association of these enlarged turbinates with acute to subacute inflammation, which is sometimes common in ferrets given live attenuated influenza virus vaccine candidates, led to this detailed microscopic evaluati ...201020837975
immune-mediated pure red cell aplasia in a domestic ferret.an 8-month-old spayed female domestic ferret (mustela putorius furo) was referred for examination to determine the cause of lethargy and severe anemia.201020839993
impact of prior seasonal influenza vaccination and infection on pandemic a (h1n1) influenza virus replication in ferrets.early epidemiologic and serologic studies have suggested pre-existing immunity to the pandemic a (h1n1) 2009 influenza virus (h1n1pdm) may be altering its morbidity and mortality in humans. to determine the role that contemporary seasonal h1n1 virus infection or trivalent inactivated vaccine (tiv) might be playing in this immunity we conducted a vaccination-challenge study in ferrets. vaccination with tiv was unable to alter subsequent morbidity or contact transmission in ferrets following chall ...201120840835
ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus a/vietnam/1203/2004 (h5n1).there is limited knowledge about the potential routes for h5n1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized h5n1 virus particles. ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. in this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized a ...201020843329
virulence-associated substitution d222g in the hemagglutinin of 2009 pandemic influenza a(h1n1) virus affects receptor binding.the clinical impact of the 2009 pandemic influenza a(h1n1) virus (pdmh1n1) has been relatively low. however, amino acid substitution d222g in the hemagglutinin of pdmh1n1 has been associated with cases of severe disease and fatalities. d222g was introduced in a prototype pdmh1n1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmh1n1 with d222g caused ocular disease in mice with ...201020844044
immunohistochemical parcellation of the ferret (mustela putorius) visual cortex reveals substantial homology with the cat (felis catus).electrophysiological mapping of the adult ferret visual cortex has until now determined the existence of 12 retinotopically distinct areas; however, in the cat, another member of the carnivora, 20 distinct visual areas have been identified by using retinotopic mapping and immunolabeling. in the present study, the immunohistochemical approach to demarcate the areal boundaries of the adult ferret visual cortex was applied in order to overcome the difficulties in accessing the sulcal surfaces of a ...201020853515
the ha and ns genes of human h5n1 influenza a virus contribute to high virulence in ferrets.highly pathogenic h5n1 influenza a viruses have spread across asia, europe, and africa. more than 500 cases of h5n1 virus infection in humans, with a high lethality rate, have been reported. to understand the molecular basis for the high virulence of h5n1 viruses in mammals, we tested the virulence in ferrets of several h5n1 viruses isolated from humans and found a/vietnam/ut3062/04 (ut3062) to be the most virulent and a/vietnam/ut3028/03 (ut3028) to be avirulent in this animal model. we then ge ...201020862325
characterization of oseltamivir-resistant 2009 h1n1 pandemic influenza a viruses.influenza viruses resistant to antiviral drugs emerge frequently. not surprisingly, the widespread treatment in many countries of patients infected with 2009 pandemic influenza a (h1n1) viruses with the neuraminidase (na) inhibitors oseltamivir and zanamivir has led to the emergence of pandemic strains resistant to these drugs. sporadic cases of pandemic influenza have been associated with mutant viruses possessing a histidine-to-tyrosine substitution at position 274 (h274y) in the na, a mutatio ...201020865125
detection and molecular characterization of mycobacterium celatum as a cause of splenitis in a domestic ferret (mustela putorius furo).mycobacterium celatum is a slow growing non-tuberculous mycobacterium described mainly as occurring in human patients. only two cases of infection with this pathogen have been reported previously in animals. a 5-year-old, neutered male ferret was presented with progressive weight loss and muscle atrophy. pale mucous membranes, slight alopecia of the tail and splenomegaly, confirmed by abdominal ultrasound, were observed. fine-needle aspirations of the spleen revealed extramedullary haematopoiesi ...201020880545
predator odor avoidance as a rodent model of anxiety: learning-mediated consequences beyond the initial exposure.prey animals such as rats display innate defensive responses when exposed to the odor of a predator, providing a valuable means of studying the neurobiology of anxiety. while the unconditioned behavioral and neural responses to a single predator odor exposure have been well documented, the paradigm can also be used to study learning-dependent adaptations that occur following repeated exposure to a stressor or associated stimuli. in developing preclinical models for human anxiety disorders this i ...201020884366
a new method to measure cortical growth in the developing brain.folding of the cerebral cortex is a critical phase of brain development in higher mammals but the biomechanics of folding remain incompletely understood. during folding, the growth of the cortical surface is heterogeneous and anisotropic. we developed and applied a new technique to measure spatial and directional variations in surface growth from longitudinal magnetic resonance imaging (mri) studies of a single animal or human subject. mri provides high resolution 3d image volumes of the brain a ...201020887014
classical swine h1n1 influenza viruses confer cross protection from swine-origin 2009 pandemic h1n1 influenza virus infection in mice and ferrets.the hemagglutinin of the 2009 pandemic h1n1 influenza virus is a derivative of and is antigenically related to classical swine but not to seasonal human h1n1 viruses. we compared the a/california/7/2009 (ca/7/09) virus recommended by the who as the reference virus for vaccine development, with two classical swine influenza viruses a/swine/iowa/31 (sw/ia/31) and a/new jersey/8/1976 (nj/76) to establish the extent of immunologic cross-reactivity and cross-protection in animal models. primary infec ...201020926110
ns-based live attenuated h1n1 pandemic vaccines protect mice and ferrets.although vaccines against influenza a virus are the most effective method to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. we generated live attenuated human influenza a vaccines (laivs) by rationally engineering mutations directly into the genome of a pandemic-h1n1 virus. two laivs (ns1-73 and ns1-126) were based on the success of laivs for animal influenza a viruses. a third candidate (nsδ5) is a unique ns-mutant that has never been us ...201020934458
feasibility of single-shot h5n1 influenza vaccine in ferrets, macaques and rabbits.the feasibility of a single-shot, low-dose vaccination against pandemic influenza was investigated. the immunogenicity and safety of whole inactivated, cell culture-derived h5n1 virus plus covaccine ht™ as adjuvant was tested in various animal species. in ferrets, doses of 4.0 and 7.5 μg h5n1 (nibrg-14; a/vietnam/1194/04; clade 1) without adjuvant gave low geometric mean haemagglutination inhibition (hi) titres (gmts) of 21-65 three weeks after intramuscular (im) injection. the addition of 0.25- ...201020950729
rapid detection of the pandemic 2009 h1n1 virus m gene by real-time and gel-based rt-pcr assays.since the first pandemic 2009 h1n1 (ph1n1) virus was isolated from humans, it has also been detected in other mammalian (pigs, cats, dogs, ferrets) and avian (turkey) species, most likely because of cross-species transmission from humans. the ph1n1 contains six genes derived from swine influenza viruses (sivs) currently circulating in north america of human- (pb1), avian- (pb2, pa), and swine- (ha, np, and ns) origin and two genes (na and m) derived from eurasian sivs. the novel genetic composit ...201020958934
pcpp-formulated h5n1 influenza vaccine displays improved stability and dose-sparing effect in lethal challenge studies.the potential impact of an influenza pandemic can be mitigated through the realization of a successful vaccination program. the implementation of antigen stabilization and dose-sparing technologies is an important step in improving availability of vaccines at the time of a pandemic outbreak. we investigated poly[di(carboxylatophenoxy)phosphazene] (pcpp) as a potential stabilizing and immunostimulating agent for h5n1 influenza vaccine. physicochemical characterization of pcpp-formulated h5n1 infl ...201120960569
contemporary seasonal influenza a (h1n1) virus infection primes for a more robust response to split inactivated pandemic influenza a (h1n1) virus vaccination in ferrets.human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. in april 2009, cases of a novel h1n1 influenza virus in children in the southwestern united states were reported. it was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in mexico. the emergence of the pandemic led to a number of national vaccination programs. surprisingl ...201020962210
characterization of vocal fold scar formation, prophylaxis, and treatment using animal models.to review recent literature on animal models used to study the pathogenesis, detection, prevention, and treatment of vocal fold scarring. animal work is critical to studying vocal fold scarring because it is the only way to conduct systematic research on the biomechanical properties of the layered structure of the vocal fold lamina propria, and therefore develop reliable prevention and treatment strategies for this complex clinical problem.201020962643
epidural anesthesia and analgesia in ferrets.anesthesia and analgesia should be provided to ferrets that are undergoing potentially painful surgical procedures. the epidural route of administration for anesthetic or analgesic drugs can be used. this column outlines the relevant ferret anatomy, indications and contraindications and technique of epidural administration of anesthesia and analgesia in ferrets.201020962759
[not available]. 194621025405
early gene expression events in ferrets in response to sars coronavirus infection versus direct interferon-alpha2b stimulation.type i interferons (ifns) are essential to the clearance of viral diseases, however, a clear distinction between genes upregulated by direct virus-cell interactions and genes upregulated by secondary ifn production has not been made. here, we investigated differential gene regulation in ferrets upon subcutaneous administration of ifn-α2b and during sars-cov infection. in vivo experiments revealed that ifn-α2b causes stat1 phosphorylation and upregulation of abundant ifn response genes (irgs), ch ...201021035159
replication and pathogenesis of the pandemic (h1n1) 2009 influenza virus in mammalian models.this study aimed to characterize the replication and pathogenic properties of a korean pandemic (h1n1) 2009 influenza virus isolate in ferrets and mice. ferrets infected with a/korea/01/2009 (h1n1) virus showed mild clinical signs. the virus replicated well in lungs and slightly in brains with no replication in any other organs. severe bronchopneumonia and thickening of alveolar walls were detected in the lungs. viral antigens were detected in the bronchiolar epithelial cells, in peribronchial g ...201021046344
diffusion tensor imaging detects early cerebral cortex abnormalities in neuronal architecture induced by bilateral neonatal enucleation: an experimental model in the ferret.diffusion tensor imaging (dti) is a technique that non-invasively provides quantitative measures of water translational diffusion, including fractional anisotropy (fa), that are sensitive to the shape and orientation of cellular elements, such as axons, dendrites and cell somas. for several neurodevelopmental disorders, histopathological investigations have identified abnormalities in the architecture of pyramidal neurons at early stages of cerebral cortex development. to assess the potential ca ...201021048904
universality in the evolution of orientation columns in the visual cortex.the brain's visual cortex processes information concerning form, pattern, and motion within functional maps that reflect the layout of neuronal circuits. we analyzed functional maps of orientation preference in the ferret, tree shrew, and galago--three species separated since the basal radiation of placental mammals more than 65 million years ago--and found a common organizing principle. a symmetry-based class of models for the self-organization of cortical networks predicts all essential featur ...201021051599
populations of radial glial cells respond differently to reelin and neuregulin1 in a ferret model of cortical dysplasia.radial glial cells play an essential role during corticogenesis through their function as neural precursors and guides of neuronal migration. both reelin and neuregulin1 (nrg1) maintain the radial glial scaffold; they also induce expression of brain lipid binding protein (blbp), a well known marker of radial glia. although radial glia in normal ferrets express both vimentin and blbp, this coexpression diverges at p3; vimentin is expressed in the radial glial processes, while blbp appears in cell ...201021060844
[recent developments in sars vaccine studies.]severe acute respiratory syndrome (sars) caused thousands of human infections worldwide and hundreds of deaths in just a few months. evidence indicates that sars coronavirus (sars-cov) has been circulating from animals to humans since before the 2002-2003 outbreak, suggesting that another pandemic may occur. this possibility has focused continuous action on sars vaccine research. inactivated vaccines, viral and bacterial vector vaccines, recombinant protein vaccines, subunit vaccines, dna vaccin ...201021064002
circulating antibodies and the resistance of ferrets to reinfection with influenza virus. 194621064615
the receptor-binding domain of influenza virus hemagglutinin produced in escherichia coli folds into its native, immunogenic structure.the hemagglutinin (ha) surface glycoprotein promotes influenza virus entry and is the key protective antigen in natural immunity and vaccines. the ha protein is a trimeric envelope glycoprotein consisting of a globular receptor-binding domain (ha-rbd) that is inserted into a membrane fusion-mediating stalk domain. similar to other class i viral fusion proteins, the fusogenic stalk domain spontaneously refolds into its postfusion conformation when expressed in isolation, consistent with this doma ...201021068239
pain management in ferrets.the growing popularity of ferrets as pets has created the demand for advanced veterinary care for these patients. pain is associated with a broad range of conditions, including acute or chronic inflammatory disease, neoplasia, and trauma, as well as iatrogenic causes, such as surgery and diagnostic procedures. effective pain management requires knowledge and skills to assess pain, good understanding of the pathophysiology of pain, and general knowledge of pharmacologic and pharmacodynamic princi ...201121074706
enzymatic formation of apo-carotenoids from the xanthophyll carotenoids lutein, zeaxanthin and β-cryptoxanthin by ferret carotene-9',10'-monooxygenase.xanthophyll carotenoids, such as lutein, zeaxanthin and β-cryptoxanthin, may provide potential health benefits against chronic and degenerative diseases. investigating pathways of xanthophyll metabolism are important to understanding their biological functions. carotene-15,15'-monooxygenase (cmo1) has been shown to be involved in vitamin a formation, while recent studies suggest that carotene-9',10'-monooxygenase (cmo2) may have a broader substrate specificity than previously recognized. in this ...201021081106
bacterial ha1 vaccine against pandemic h5n1 influenza virus: evidence of oligomerization, hemagglutination, and cross-protective immunity in ferrets.the impending influenza virus pandemic requires global vaccination to prevent large-scale mortality and morbidity, but traditional influenza virus vaccine production is too slow for rapid responses. we have developed bacterial systems for expression and purification of properly folded functional hemagglutinin as a rapid response to emerging pandemic strains. a recombinant h5n1 (a/vietnam/1203/2004) hemagglutinin globular domain (ha1) was produced in escherichia coli under controlled redox refold ...201021084473
antibody responses induced by japanese whole inactivated vaccines against equine influenza virus (h3n8) belonging to florida sublineage clade2.in 2010, the world organisation for animal health recommended the inclusion of a florida sublineage clade2 strain of equine influenza virus (h3n8), which is represented by a/equine/richmond/1/07 (richmond07), in equine influenza vaccines. here, we evaluate the antigenic differences between japanese vaccine strains and richmond07 by performing hemagglutination inhibition (hi) assays. ferret antiserum raised to a/equine/la plata/93 (la plata93), which is a japanese vaccine strain, reacted with ric ...201021099188
immunogenicity and protective efficacy of a live attenuated vaccine against the 2009 pandemic a h1n1 in mice and ferrets.a novel 2009 influenza a (h1n1) virus was transmitted from humans to humans worldwide. the live attenuated monovalent a h1n1 vaccine (lamv) for intranasal administration has shown promising immunogenicity and safety in clinical trials and for human use, but the experimental data based on lamv is incomplete. in this study, using reverse genetic technology, we produced a cold-adapted (ca), live attenuated bj/aa ca that contained hemagglutinin (ha) and neuraminidase (na) genes from a 2009 pandemic ...201021111782
does pandemic a/h1n1 virus have the potential to become more pathogenic?epidemiologic observations that have been made in the context of the current pandemic influenza virus include a stable virulence phenotype and a lack of propensity to reassort with seasonal strains. in an attempt to determine whether either of these observations could change in the future, we coinfected differentiated human airway cells with seasonal oseltamivir-resistant a/new jersey/15/07 and pandemic a/tennessee/1-560/09 (h1n1) viruses in three ratios (10:90, 50:50, and 90:10) and examined th ...201021116343
effects of the new benzimidazole derivative tas-203, an orally active phosphodiesterase 4 inhibitor, on airway inflammation in rats and emetic responses in ferrets.tas-203 (2-[3-(cyclopropylmethoxy)-4-methoxyphenyl]-5-(1h-1,2,4-triazol-1-yl)-1h-benzimidazole, cas 223909-92-0) is a novel phosphodiesterase 4 (pde4) inhibitor that has been found to have good anti-inflammatory effects and low emetogenic activity in vivo. in the present studies, the anti-inflammatory profile of tas-203 was examined and compared with that of cilomilast (cas 153259-65-5), the most advanced pde4 inhibitor. tas-203 inhibited the activity of purified human pde4 with an ic50 value of ...201021117500
a novel sequence-based antigenic distance measure for h1n1, with application to vaccine effectiveness and the selection of vaccine strains.h1n1 influenza causes substantial seasonal illness and was the subtype of the 2009 influenza pandemic. precise measures of antigenic distance between the vaccine and circulating virus strains help researchers design influenza vaccines with high vaccine effectiveness. we here introduce a sequence-based method to predict vaccine effectiveness in humans. historical epidemiological data show that this sequence-based method is as predictive of vaccine effectiveness as hemagglutination inhibition assa ...201021123189
pathogenesis and transmission of triple-reassortant swine h1n1 influenza viruses isolated before the 2009 h1n1 pandemic.the 2009 h1n1 pandemic influenza virus represents the greatest incidence of human infection with an influenza virus of swine origin to date. moreover, triple-reassortant swine (trs) h1n1 viruses, which share similar host and lineage origins with 2009 h1n1 viruses, have been responsible for sporadic human cases since 2005. similar to 2009 h1n1 viruses, trs viruses are capable of causing severe disease in previously healthy individuals and frequently manifest with gastrointestinal symptoms; howeve ...201021123386
genetic immunization in the lung induces potent local and systemic immune responses.successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. to accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver replication-incompetent recombinant adenoviral vectors expressing gene products from several infectious pathogens. we show that this regimen induced remarkably high and stable lung t-cell responses in nonhuman pr ...201021135247
pandemic influenza 1918 h1n1 and 1968 h3n2 dna vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades.alternative influenza vaccines and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross-reactivity against drifted strains. furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change in the vaccine formulations.201021138536
echocardiographic and electrocardiographic examination of clinically healthy, conscious ferrets.to assess the feasibility of performing electrocardiography (ecg) and echocardiography on conscious ferrets and to establish reference values for this species under these conditions.201121143233
seasonal influenza vaccination and the risk of infection with pandemic influenza: a possible illustration of non-specific temporary immunity following infection.four canadian studies have suggested that receipt of seasonal influenza vaccine increased the risk of laboratory-confirmed infection with 2009 pandemic influenza a(h1n1). during the influenza season of 2009 in victoria, australia, this virus comprised 97% of all circulating influenza viruses for which sub-typing was available. we found no evidence that seasonal influenza vaccine increased the risk of, or provided protection against, infection with the pandemic virus. ferret experiments have sugg ...201021144441
a motion direction map in macaque v2.in mammals, the perception of motion starts with direction-selective neurons in the visual cortex. despite numerous studies in monkey primary and second visual cortex (v1 and v2), there has been no evidence of direction maps in these areas. in the present study, we used optical imaging methods to study the organization of motion response in macaque v1 and v2. in contrast to the findings in other mammals (e.g., cats and ferrets), we found no direction maps in macaque v1. robust direction maps, ho ...201021145011
activation of phenotypically-distinct neuronal subpopulations of the rat amygdala following exposure to predator odor.exposure of rats to an odor of a predator can elicit an innate fear response. in addition, such exposure has been shown to activate limbic brain regions such as the amygdala. however, there is a paucity of data on the phenotypic characteristics of the activated amygdalar neurons following predator odor exposure. in the current experiments, rats were exposed to cloth which contained either ferret odor, butyric acid, or no odor for 30 min. ferret odor-exposed rats displayed an increase in defensiv ...201021146592
[study on the status of infection and distribution of rabies virus in china.]objective: to investigate the status of infection and distribution of rabies virus (rv) in different epidemic areas in china. methods: brain specimens from animals and suspected patients were collected at the districts of high-, medium- and low incidence rates of human rabies and detected by both direct immunofluorescence assay (dfa) and rt-pcr. results: 254 of 3007 specimens of dog brains showed rv positive by dfa (positive rate of 8.4%). among these 254 samples, 78 showed positive (positive ra ...201021163029
feasibility of reconstructed ancestral h5n1 influenza viruses for cross-clade protective vaccine development.since the reemergence of highly pathogenic h5n1 influenza viruses in humans in 2003, these viruses have spread throughout avian species in asia, europe, and africa. their sustained circulation has resulted in the evolution of phylogenetically diverse lineages. viruses from these lineages show considerable antigenic variation, which has confounded vaccine planning efforts. we reconstructed ancestral protein sequences at several nodes of the hemagglutinin (ha) and neuraminidase (na) gene phylogeni ...201021173241
urethral catheterization of the male ferret for treatment of urinary tract obstruction.male ferrets are used in various biomedical research studies and generally thrive in laboratory conditions. urethral obstruction can occur in male ferrets of all ages, and urethral catheterization may be needed to relieve the obstruction. this column describes urinary catheter selection, placement and monitoring in the male ferret.201121173771
catastrophes in wavefront-coding spatial-domain design.spatial-domain design for wavefront-coding systems frequently simplifies the defining oscillatory integral of the point spread function (psf) by means of the stationary phase approximation (spa). although the spa applies over much of the support of the psf, it tends to break down at or near the regions of highest intensity. a branch of mathematics known as catastrophe theory is shown to provide tools that can ferret out important design information precisely at the points where the spa is unphys ...201021173823
preclinical and clinical development of plant-made virus-like particle vaccine against avian h5n1 influenza.the recent swine h1n1 influenza outbreak demonstrated that egg-based vaccine manufacturing has an achille's heel: its inability to provide a large number of doses quickly. using a novel manufacturing platform based on transient expression of influenza surface glycoproteins in nicotiana benthamiana, we have recently demonstrated that a candidate virus-like particle (vlp) vaccine can be generated within 3 weeks of release of sequence information. herein we report that alum-adjuvanted plant-made vl ...201021203523
in vivo characterization of gsk256066, a high-affinity inhaled phosphodiesterase 4 inhibitor.oral phosphodiesterase (pde) 4 inhibitors have demonstrated clinical efficacy in chronic obstructive pulmonary disease and asthma. preclinical and clinical investigation of inhaled pde4 inhibitors is ongoing. 6-({3-[(dimethylamino)carbonyl]phenyl}sulfonyl)-8-methyl-4-{[3-methyloxy)phenyl]amino}-3-quinolinecarboxamide (gsk256066) is an exceptionally high-affinity and selective inhibitor of pde4 designed for inhaled delivery. the aim of these studies was to investigate the potency, duration of act ...201121205924
multidrug-resistant 2009 pandemic influenza a(h1n1) viruses maintain fitness and transmissibility in ferrets.the 2009 influenza a(h1n1) pandemic called attention to the limited influenza treatment options available, especially in individuals at high risk of severe disease. neuraminidase inhibitor-resistant seasonal h1n1 viruses have demonstrated the ability to transmit well despite early data indicating that resistance reduces viral fitness. 2009 h1n1 pandemic viruses have sporadically appeared containing resistance to neuraminidase inhibitors and the adamantanes, but the ability of these viruses to re ...201021208927
efficacy of vaccination with different combinations of mf59-adjuvanted and nonadjuvanted seasonal and pandemic influenza vaccines against pandemic h1n1 (2009) influenza virus infection in ferrets.serum antibodies induced by seasonal influenza or seasonal influenza vaccination exhibit limited or no cross-reactivity against the 2009 pandemic swine-origin influenza virus of the h1n1 subtype (ph1n1). ferrets immunized once or twice with mf59-adjuvanted seasonal influenza vaccine exhibited significantly reduced lung virus titers but no substantial clinical protection against ph1n1-associated disease. however, priming with mf59-adjuvanted seasonal influenza vaccine significantly increased the ...201121209108
cellular immune response in the presence of protective antibody levels correlates with protection against 1918 influenza in ferrets.the identification of immune correlates of protection against highly pathogenic human-adapted influenza is instrumental in the development of the next generation of vaccines. towards this, ferrets received either one dose of a conventionally produced vaccine, two inoculations of a hemagglutinin (ha)-expressing dna vaccine, or a prime-boost regimen of the dna vaccine followed by injection of a ha-expressing adenoviral vector. in addition to the antibody response, ferret-specific interferon-gamma ...201121211587
spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.the brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. using a bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should ...201121212356
early valproic acid exposure alters functional organization in the primary visual cortex.epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. the use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. here we investigate the effects of early exposure to valproic acid (val) and levetiracetam (lev), commonly used ant ...201121215743
vaccination against seasonal influenza a/h3n2 virus reduces the induction of heterosubtypic immunity against influenza a/h5n1 virus infection in ferrets.infection with seasonal influenza viruses induces a certain extent of protective immunity against potentially pandemic viruses of novel subtypes, also known as heterosubtypic immunity. here we demonstrate that infection with a recent influenza a/h3n2 virus strain induces robust protection in ferrets against infection with a highly pathogenic avian influenza virus of the h5n1 subtype. prior h3n2 virus infection reduced h5n1 virus replication in the upper respiratory tract, as well as clinical sig ...201121228239
vaccination with different m2e epitope densities confers partial protection against h5n1 influenza a virus challenge in chickens.objective: currently, research is focused on universal influenza vaccines based on various ectodomains of the influenza matrix protein 2 (m2e). such vaccines are tested mostly using mouse-adapted influenza viruses and in mouse or ferret models. the aim of this study was to investigate in a chicken model the protective efficacy of vaccines based on avian-type m2e at different epitope densities. methods: on the basis of the optimized avian-type m2e gene, recombinant plasmids that contained tandem ...201121228535
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